Cocaine (COC) and methamphetamine (MTH) dependence have profound adverse medical, social and societal consequences. Medications development for these disorders is complicated by the fact that characteristics of COC and MTH addicts differ; the pharmacology of COC and MTH is similar, but not identical; and several agents demonstrating preliminary efficacy in COC users do not appear to be effective in MTH users. Because methodological issues may also be a factor in differential outcome, of importance is to examine medications in both COC and MTH dependent individuals in the same context. Thus, given that recent evidence suggests agents that decrease adrenergic activity may be effective in treating drug dependence, this proposal will examine the efficacy ofthe alphai- and beta-adrenergic antagonist carvedilol in delaying time to relapse in recently abstinent COC- and MTH-dependent individuals. This 12-wk, randomized, double blind, placebo-controlled clinical trial will provide treatment for 60 COC-dependent and 60 MTH-dependent (18-65 yrs) individuals over a five-year period. Participants first will reside at a residential facility (Recovery Centers of Arkansas) to initiate initial drug abstinence and be inducted on the study medication. They will be randomized by sex, severity of dependence, depressive/anxiety symptom severity and race to receive either placebo (N=30COC; N=30MTH), or carvedilol (50 mg/day; N=30COC; N=30MTH). Then participants transfer to the Outpatient Treatment Research Program and continue to receive study medication for weeks 3-12. During the outpatient portion ofthe trial, subjects participate in weekly individual cognitive behavioral therapy. During the trial, participants are given monetary incentives for complying with study requirements. At the end of 12 weeks, patients will be tapered off the study medication and referred to an appropriate treatment program. Efficacy will be determined by length of time in treatment, alleviation of withdrawal symptoms, length of time to lapse/relapse by self-report and urine toxicology, and psychosocial functioning. Prognostic relevance of factors such as sex, withdrawal symptoms, mood, genetic polymorphisms at the, e.g., alpha 1 receptor subtypes, and cognitive measures will be explored.